Review article
Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review

https://doi.org/10.1016/S0167-8140(02)00404-8Get rights and content

Abstract

Background and purpose: To determine the frequency of mucositis and associated outcomes in patients receiving radiotherapy (RT) for head and neck cancer through a systematic review of recently published literature.

Materials and methods: According to the study protocol, databases were searched for randomized clinical trials (English only, 1996–1999) of patients with head and neck cancer receiving RT with or without chemotherapy that reported one or more outcomes of interest.

Results: Thirty-three studies (n=6181 patients) met inclusion criteria. Mucositis was defined using a variety of scoring systems. The mean incidence was 80%. Over one-half of patients (56%) who received altered fractionation RT (RT-AF) experienced severe mucositis (grades 3–4) compared to 34% of patients who received conventional RT. Rates of hospitalization due to mucositis, reported in three studies (n=700), were 16% overall and 32% for RT-AF patients. Eleven percent of patients had RT regimens interrupted or modified because of mucositis in five studies (n=1267) reporting this outcome. Data insufficiency or heterogeneity prohibited analysis of mucositis severity and other associated outcomes, such as oral pain, dysphagia and opioid use.

Conclusions: Mucositis is a frequent, severe toxicity in patients treated with RT for head and neck cancer. While it appears that mucositis may lead to hospitalization and treatment interruptions, its overall impact on outcomes has not been adequately investigated.

Introduction

Growing evidence indicates more aggressive regimens improve local tumor control and survival of patients with head and neck cancer [19]. Better treatment outcomes, however, have come at the expense of increased patient morbidity, notably an increase in severe (grades 3–4) mucositis that causes substantial pain, interferes with the patient's ability to chew and swallow, and worsens the patient's quality of life [44]. Patients report that mucositis is the most debilitating side effect of their head and neck cancer therapy (Alison Rose-Ped, unpublished observations, January 1999). Management of mucositis may require feeding tube placement, hospitalization, and intensive supportive care. We undertook a systematic review of the published literature in order to better characterize the incidence and clinical and economic consequences of mucositis in the head and neck cancer population. The results may inform the design of future intervention trials for mucositis. We limited our review to ‘acute’ mucositis which occurs during or shortly after active therapy, with no intention to capture the potential delayed consequences of mucositis.

Section snippets

Search strategy

The methods of systematic review used in this study have been well described elsewhere [12], [31], [39] and include the goal of minimizing bias in the collection and interpretation of clinical data. To further minimize the possibility of bias (or appearance thereof), a firm specializing in the conduct of systematic reviews (MetaWorks Inc.) was engaged to help design the study as well as to perform the data abstraction and analysis and write a summary of the results. Medline and Current Contents

Study characteristics

Thirty-three studies (n=6181) were accepted for inclusion in the analysis (Appendix). Table 1 summarizes the study characteristics. The majority of studies (21 studies, 64%) were performed in Europe. Fifteen of the 33 studies (45%) were considered adequately powered (Level of Evidence I) even though the median quality score in these studies was only 2 (scale 1–5, mean 2.7), implying questionable internal validity. Study duration was reported in 16 studies, ranging from 1.4 to 3 months.

Treatment characteristics

Treatment

Discussion

This systematic review confirms the high incidence of mucositis in patients receiving RT, with rates of 97% reported during RT-C, 100% during RT-AF, and 89% during chemoradiation therapy. The results underscore the impact of fractionation on the severity of mucositis: 56% of patients receiving RT-AF experienced grades 3–4 mucositis, compared with 34% of patients receiving RT-C and 43% of patients on RT+CT. These rates of severe mucositis are slightly higher than, but similar to, those recently

Acknowledgements

IntraBiotics Pharmaceuticals, Inc., Mountain View, CA, USA, supported this study.

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